Staphylococcus aureus has become increasingly resistant to standard antibiotic treatment and is one of the most feared infectious pathogens as a result. The need for a safe and effective vaccine, especially for prevention of hospital-acquired infections, has grown. Nonpeptide molecules such as polysaccharide capsules, lipoteichoic acid and other lipids, are prominent features of the bacterial envelope and are often targets of the humoral immune response. The recent identification of T cells that recognize mycobacterial lipid and glycolipid antigens presented by CD1 proteins suggests that lipid-based vaccines may be effective for prevention and/or treatment of S. aureus infection. The goal of the Phase I period will be to isolate lipid fractions derived from S. aureus and to test them for their ability to stimulate the proliferation of human CD1 -restricted T cells from healthy donors. Lipids from fractions with bioactivity will be further purified and characterized. Phase II goals will be to compare the T cell responses of healthy donors with those of S. aureus patients and to utilize a model for S. aureus infection in the guinea pig to evaluate vaccine formulations containing the lipid-based antigens identified in Phase I, with other components such as adjuvants and additional antigens. PROPOSED COMMERCIAL APPLICATIONS: Staphylococcus aureus is the most common cause of nosocomial infections and is responsible for many community acquired infections such as pneumonia, septic arthritis and abscesses. Staphylococcus infections account for over a half million hospitalizations per year in the United States. An effective prophylactic or immunotherapeutic vaccine product is needed to prevent and/or treat these infections, especially because of the increase in antibiotic resistance of these organisms.